Mina Y George, Marwa O El-Derany, Yasmine Ahmed, Malvina Zaher, Caroline Ibrahim, Habiba Waleed, Hajar Khaled, Gehad Khaled, Ahmed Saleh, Huda Alshafei, Rahma Alshafei, Nirmeen Ahmed, Sara Ezz, Nouran Ashraf, Shaimaa S Ibrahim
{"title":"载金菊纳米乳抗锂/匹罗卡品致大鼠癫痫持续状态的设计与评价重点是配方、神经元兴奋毒性、氧化应激、小胶质细胞极化和AMPK/SIRT-1/PGC-1α途径。","authors":"Mina Y George, Marwa O El-Derany, Yasmine Ahmed, Malvina Zaher, Caroline Ibrahim, Habiba Waleed, Hajar Khaled, Gehad Khaled, Ahmed Saleh, Huda Alshafei, Rahma Alshafei, Nirmeen Ahmed, Sara Ezz, Nouran Ashraf, Shaimaa S Ibrahim","doi":"10.1080/17425247.2023.2153831","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>The present study aims to formulate and evaluate the efficacy of chrysin-loaded nanoemulsion (CH NE) against lithium/pilocarpine-induced epilepsy in rats, as well as, elucidate its effect on main epilepsy pathogenesis cornerstones; neuronal hyperactivity, oxidative stress, and neuroinflammation.</p><p><strong>Methods: </strong>NEs were characterized by droplet size, zeta potential, pH, in vitro release, accelerated and long-term stability studies. Anti-convulsant efficacy of the optimized formula and underlying mechanisms involved were assessed and compared to that from CH suspension given orally at a 30 folds higher dose.</p><p><strong>Results: </strong>Optimized formula displayed a droplet size of 48.09 ± 0.83 nm, PDI 0.25 ± 0.011, sustained release, and good stability. CH treatment reduced seizures scoring, corrected behavioral and histological changes induced by Li/Pilo. Moreover, CH restored neurotransmitters balance and oxidative stress markers levels. Besides, CH induced microglia polarization from M1 to M2 hindering inflammation induced by Li/Pilo. Also, CH restored energy metabolism homeostasis via regulating protein expression of AMPK/SIRT-1/PGC-1α pathway markers. CH NE formulation was found to significantly enhance drug delivery to rats' hippocampus compared to CH suspension.</p><p><strong>Conclusion: </strong>Our findings prove the therapeutic efficacy of CH NE at a lower dose which could be a potential brain targeting platform to combat epilepsy.</p>","PeriodicalId":12229,"journal":{"name":"Expert Opinion on Drug Delivery","volume":null,"pages":null},"PeriodicalIF":5.0000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"7","resultStr":"{\"title\":\"Design and evaluation of chrysin-loaded nanoemulsion against lithium/pilocarpine-induced status epilepticus in rats; emphasis on formulation, neuronal excitotoxicity, oxidative stress, microglia polarization, and AMPK/SIRT-1/PGC-1α pathway.\",\"authors\":\"Mina Y George, Marwa O El-Derany, Yasmine Ahmed, Malvina Zaher, Caroline Ibrahim, Habiba Waleed, Hajar Khaled, Gehad Khaled, Ahmed Saleh, Huda Alshafei, Rahma Alshafei, Nirmeen Ahmed, Sara Ezz, Nouran Ashraf, Shaimaa S Ibrahim\",\"doi\":\"10.1080/17425247.2023.2153831\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>The present study aims to formulate and evaluate the efficacy of chrysin-loaded nanoemulsion (CH NE) against lithium/pilocarpine-induced epilepsy in rats, as well as, elucidate its effect on main epilepsy pathogenesis cornerstones; neuronal hyperactivity, oxidative stress, and neuroinflammation.</p><p><strong>Methods: </strong>NEs were characterized by droplet size, zeta potential, pH, in vitro release, accelerated and long-term stability studies. Anti-convulsant efficacy of the optimized formula and underlying mechanisms involved were assessed and compared to that from CH suspension given orally at a 30 folds higher dose.</p><p><strong>Results: </strong>Optimized formula displayed a droplet size of 48.09 ± 0.83 nm, PDI 0.25 ± 0.011, sustained release, and good stability. CH treatment reduced seizures scoring, corrected behavioral and histological changes induced by Li/Pilo. Moreover, CH restored neurotransmitters balance and oxidative stress markers levels. Besides, CH induced microglia polarization from M1 to M2 hindering inflammation induced by Li/Pilo. Also, CH restored energy metabolism homeostasis via regulating protein expression of AMPK/SIRT-1/PGC-1α pathway markers. CH NE formulation was found to significantly enhance drug delivery to rats' hippocampus compared to CH suspension.</p><p><strong>Conclusion: </strong>Our findings prove the therapeutic efficacy of CH NE at a lower dose which could be a potential brain targeting platform to combat epilepsy.</p>\",\"PeriodicalId\":12229,\"journal\":{\"name\":\"Expert Opinion on Drug Delivery\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.0000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"7\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Expert Opinion on Drug Delivery\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/17425247.2023.2153831\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert Opinion on Drug Delivery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/17425247.2023.2153831","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Design and evaluation of chrysin-loaded nanoemulsion against lithium/pilocarpine-induced status epilepticus in rats; emphasis on formulation, neuronal excitotoxicity, oxidative stress, microglia polarization, and AMPK/SIRT-1/PGC-1α pathway.
Objectives: The present study aims to formulate and evaluate the efficacy of chrysin-loaded nanoemulsion (CH NE) against lithium/pilocarpine-induced epilepsy in rats, as well as, elucidate its effect on main epilepsy pathogenesis cornerstones; neuronal hyperactivity, oxidative stress, and neuroinflammation.
Methods: NEs were characterized by droplet size, zeta potential, pH, in vitro release, accelerated and long-term stability studies. Anti-convulsant efficacy of the optimized formula and underlying mechanisms involved were assessed and compared to that from CH suspension given orally at a 30 folds higher dose.
Results: Optimized formula displayed a droplet size of 48.09 ± 0.83 nm, PDI 0.25 ± 0.011, sustained release, and good stability. CH treatment reduced seizures scoring, corrected behavioral and histological changes induced by Li/Pilo. Moreover, CH restored neurotransmitters balance and oxidative stress markers levels. Besides, CH induced microglia polarization from M1 to M2 hindering inflammation induced by Li/Pilo. Also, CH restored energy metabolism homeostasis via regulating protein expression of AMPK/SIRT-1/PGC-1α pathway markers. CH NE formulation was found to significantly enhance drug delivery to rats' hippocampus compared to CH suspension.
Conclusion: Our findings prove the therapeutic efficacy of CH NE at a lower dose which could be a potential brain targeting platform to combat epilepsy.
期刊介绍:
Expert Opinion on Drug Delivery (ISSN 1742-5247 [print], 1744-7593 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles covering all aspects of drug delivery research, from initial concept to potential therapeutic application and final relevance in clinical use. Each article is structured to incorporate the author’s own expert opinion on the scope for future development.